AUTHOR=Huang Yunqi , Liu Yunjia , Wu Yulu , Tang Yiguo , Zhang Mengting , Liu Siyi , Xiao Liling , Tao Shiwan , Xie Min , Dai Minhan , Li Mingli , Gui Hongsheng , Wang Qiang 

TITLE=Patterns of Convergence and Divergence Between Bipolar Disorder Type I and Type II: Evidence From Integrative Genomic Analyses

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.956265

DOI=10.3389/fcell.2022.956265

ISSN=2296-634X

ABSTRACT=Aims: Genome wide association studies (GWAS) analyses have revealed genetic evidence of bipolar disorder (BD), but little is known about genetic structure of BD subtypes. We aimed to investigate genetic overlap and distinction of bipolar type I (BD I) & type II (BD II) by conducting integrative post-GWAS analyses. 
Methods: We utilized single nucleotide polymorphism (SNP)-level approaches to uncover correlated and distinct genetic loci. Transcriptome-wide association analyses (TWAS) were then approached to pinpoint functional genes expressed in specific brain tissues and blood. Next, we performed cross-phenotype analysis including exploring the potential causal associations between BD I&II and lithium responses and comparing the difference of genetic structures among four different psychiatric traits.
Results: SNP-level evidence revealed three genomic loci, SLC25A17, ZNF184 and RPL10AP3 shared by BD I & II, and one locus (i.e., MAD1L1) and significant gene sets involved in calcium channel activity, neural and synapsed signals that distinguished two subtypes. TWAS data implicated different genes effecting BD I & II through expression in specific brain regions (e.g., nucleus accumbens for BD I). Cross-phenotype analyses indicated that BD I&II share continuous genetic structures with schizophrenia (SCZ) and major depression disorder (MDD), which help fill the gaps left by the dichotomy of mental disorder.
Conclusions: These combined evidences illustrate genetic convergence and divergence between BD I & II and provide an underlying biological and trans-diagnostic insight into major psychiatric disorders.